We have recently shown that IgA immune complexes can cause acute injury in rat lung. Whether a similar mechanism pertains in human interstitial lung diseases is not known, although IgA immune complex injury represents a significant problem in human renal glomerular and vascular diseases. Lung injury produced by IgA immune complexes has been found to be dependent on complement but independent of neutrophils, whereas IgG immune complex injury requires both mediator systems. We will measusre in vitro the production of oxygen radicals in both rat neutrophils and alveolar macrophages using a variety of agonists, including IgG and IgA immune complexes. Additional parameters of cell activation to be employed will include enzyme secretion and generation of arachidonate products. We will also explore the ability of complement activation products to "potentiate" phagocytic cells for O2-. production stimulated by IgG and IgA immune complexes. These studies will be aided by the use of highly sensitive flow cytometric techniques. A series of in vivo studies will be carried out in order to determine if oxygen radicals participate in IgA-immune complex induced acute lung injury and, if so, what types of oxygen products are involved. We will take advantage of recent studies in which we have developed a series of interventions designed to define the role of oxygen radicals and to characterize, to the extent possible, the nature of the radical involved. In vivo studies will also be done to determine if products of arachidonic acid are involved in the tissue injury. Finally, phagocytic cells retrieved from IgG and IgA immune complex injured lungs will be examined in vitro for spontaneous as well as stimulated production of oxygen radicals. These studies should provide additional information on the role of oxygen radicals in IgA immune complex induced injury and should lead to a better understanding of the way in which IgA immune complexes bring about tissue injury.